The purpose of this renewal program is to continue the study of injury and repair of the lung specifically as related to the development of experimental emphysema. The current studies to be performed are concerned with the early effects of intravenously administered elastase. We will concentrate efforts on study of the early changes utilizing both pressure volume measurements of the excised lung and ultrastructural studies of the elastin fibers and network. The models of elastase induced emphysema up until now have depended upon the introduction of purified elastase. We have initiated studies to stimulate and concentrate large numbers of autologous leucocytes. These leukocytes contain elastase which will be introduced into the respiratory tract of the animals from which they were harvested in attempts to produce emphysema experimentally. The effects of these leukocytes on the elastic fibers of the autoloous lung (in vivo) will be studied by SEM and TEM microscopy. Studies of the lung and bronchus in organ culture will be continued to evaluate the morphologic and biochemical effects of antioxidant materials on the epithelial and glandular structures. Biochemical analyses of the culture fluid and tissue for hexosamine, sialic acid, protein and lysozyme will be performed. We will continue comparative studies of the histological and morphometric changes induced by NO2 inhalation in contrast to methacholine stimulation on the mucous cells of the epithelium and gland of the tracheobronchial tree of a cat. BIBLIOGRAPHIC REFERENCES: Niewoehner, D.E., Kleinerman, J., and Liotta, L.A.: Elastic behavior of postmortem human lungs: Effects of aging and mild emphysema. J. Appl. Physiol. 39: 943, 1975. Schuyler, M., Niewoehner, D.E., and Kleinerman, J.: Biopsy confirmed sarcoidal interstitial fibrosis after a fifteen year remission. Ohio State Med. Journal. 71: 707, 1975.